Aminoacetamidoximic quaternary ammonium compounds



United fli fis Patent t AMINOACETAMID OXIMIC QUATERNARY AMMONIUMCOMPOUNDS Peter L. de Benneville, Philadelphia, Pa., assignor to Rohm &Haas Company, Philadelphia, Pa., a corporation of Delaware No Drawing.Filed Dec. 23, 1957, Ser. No. 704,332

6 Claims. (Cl. 260-4475) This invention deals with aminoacetamidoximicquaternary ammonium compounds as new compositions of matter. It furtherconcerns a method for the preparation of these compounds.

The compounds of the present invention may be represented by the formulaThe symbol R may represent bon atoms in which the alkoxy group oralkenoxy group i is no closer than the beta position with respect to theamino nitrogen atom, a hydroxyalkyl group of two to eighteen carbonatoms in which the hydroxy group is no closer than the beta positionwith respect to the amino nitrogen atom, an alkoxyarylalkyl,aryloxyalkyl, or alkylaryloxyalkyl group of no more than twenty-one car-'bon atoms, an arylalkyl group of seven to twenty-one carbon atoms,alkylarylalkyl group of eight to twentyone carbon atoms, or arylalkenylgroup of eight to twenty-one carbon atoms, arylalkyl groups havinghalogen or nitro substituents, a carbamoylalkyl group of two to eighteencarbon atoms, an alkoxycarbonylalkyl or acyloxyalkyl group of three totwenty carbon atoms, and

an alkylcarbonylalkyl group of three to twenty carbon atoms orarylcarbonylalkyl group of eight to twenty carbon atoms.

The symbol R may exhibit all of the possible configurations andstructures. Substituents in the group R may occupy any of the possiblestructural locations.

The symbol m represents an integer of one to two, preferably one.

The symbol X repre ents an anion. In this respect, there may be usedchloride, bromide, iodide, sulfate, methosulfate, phosphate, acetate,lactate, hydroxide, tartrate, thiocyanate, nitrate, pentachlorophenate,and the like. The halogens having an atomic weight of about 35.5 to 127are preferred. Anions other than the halogens or the hydroxide may besupplied directly or by metathesis with the halide or hydroxide form ofthe present quaternary ammonium compounds. An anion exchange resin mayalso be used to supply the desired ion. It will be apparent to oneskilled in the art that the identity of the cationic portion of thepresent compounds is the critic-al consideration and that the anionic-'portion is relatively unimportant.

r, 2,970,145 Patented Jan. 31, 1961 Typical of the groups that R mayrepresent include methyl, ethyl, propyl, butyl, pentyl, hexyl, octyl,nonyl, decyl, dodecyl, pentadecyl, octadecyl; allyl, methallyl, butenyl,pentenyl, hexenyl, octenyl, decenyl, dodecenyl, tetradecenyl,octadecenyl, propynyl, butynyl, pentynyl, hexynyl, octynyl, decynyl,dodecynyl, octadecynyl; methoxyethyl, methoxybutyl, methoxypentyl,methoxyoctyl, methoxyldecyl, methoxydodecyl, methoxyoctadecyl,ethoxyethyl, ethoxypropyl, ethoxyhexyl, ethoxynonyl, ethoxydecyl,ethoxytetradecyl, ethoxyoctadecyl, propoxyethyl, propoxypropyl,propoxyheptyl, propoxydecyl, propoxytetradecyl, propoxyheptadecyl,butoxyethyl, butoxy butyl, butoxyoctyl, butoxyundecyl, butoxyhexadecyl,pentoxyethyl, pentoxypentyl, pentoxyhexyl, pentoxypentadecyl,hexoxyethyl, hexoxybutyl, hexoxyhexyl, hexoxydodecyl, hexoxytetradecyl,heptoxyethyl, heptoxyheptyl, heptoxydodecyl, octoxyethyl, octoxypropyl,octoxybutyl, octoxyoctyl, octoxydecyl, nonoxyethyl, nonoxypentyl,nonoxynonyl, nonoxydecyl, decoxyethyl, decoxypropyl, decoxypentyl,decoxydecyl, undecoxyethyl, undecoxyheptyl, dodecoxyethyl,dodecoxypentyl, dodecoxyoctyl, tridecoxytheyl, tridecoxyheptyl,tetradecoxyethyl, tetradecoxybutyl, pentadecoxyethyl, pentadecoxypentyl,hexadecoxyethyl, heptadecoxyethyl, octadecoxyethyl, vinoxyethyl,vinoxybutyl, vinoxyoctyl, vinoxydecyl, vinoxydodecyl, vinoxyoctadecyl,alloxyethyl, alloxypropyl, alloxynonyl, alloxytetradecyl, butenoxyethyl,butenoxypentyl, butenoxyheptyl, butenoxyundecyl, butenoxytetradecyl,pentenoxyethyl, pentenoxypentyl, pentenoxydodecyl, pentenoxytridecyl,hexenoxyethyl, hexenoxyhexyl, hexenoxynonyl, hexenoxytetradecyl,nonenoxyethyl, nonenoxypentyl, nonenoxyhexyl, nonenoxynonyl,decenoxyethyl, decenoxyoctyl, undecenoxyethyl, undeeenoxyoctvl,dodecenoxyethyl, dodecenoxypentyl, tridecenoxyethyl, tridecenoxyheptyl,tetradecenoxyethyl, tetradecenoxybutyl, pentadecenoxyethyl,pentadeeenoxypentyl, hexadecenoxyethyl, heptadecenoxyethyl,octadecenoxyethyl; hydroxyethyl, hydroxypropyl, hydroxybutyl,hydroxypentyl, hydroxyoctyl, hydroxydecyl, hydroxydodecyl,hydroxyoctadecyl; benzyl,.butylbenzyl, octylbenzyl, dodecylbenzyl,dimethylbenzyl, methylbutylbenzyl, dihexylbenzyl, phenylethyl,butylphenylethyl, phenylbutyl, phenyldodecyl, naphthylethyl,naphthylbutyl, naphthyloctyl, phenylbutenyl, phenyloctenyl,phenyldecenyl,

phenyldodecenyl, octylphenylbutenyl; chlorobenzyl, dichlorobenzyl,bromobenzyl, cyanobenzyl, nitrobenzyl;

tridecylcarbonylmethyl, tetradecylcarbonylethyl, penta-"decycicarbonylpropyl, hexadecylcarbonylheptyl, hepta-'decylcarbouylbutyl, octadecylcarbonylethyl, phenylcarbonylmethyl,phenylcarbonylethyl, phenylcarbonylpropyl, phenylcarbonylbutyl,phenylcarbonyloctyl, phenylcarbonyldecyl, phenylcarbonyldo-decyl,phenylcarbonyltetradecyl, phenylcarbonylheptadecyl,napthylcarbonylmethyl, naphthylcarbonylethyl, naphthylcarbonylpentyl,naphthylcarbonyloctyl, naphthylcarbonyldodecyl, naphthylcarbonyltridecyl, butylphenylcarbonylo ctyl, ethylnaphthylcarbonylhexyl,and octylphenylcarbonylpentyl. The compounds of this invention areproduced by bringing together in a reacting temperature and therebyeffecting quaternization a compound having the formula "R X, with acompound having the formula R NOH in which the symbols have thesignificance previously referred to. The aminoalkanamidoxime reactantsare prepared according to the'method disclosed in United Statesapplication Serial Number 704,331, filed December 23, 1957.

Typical representations of the R X reactants, illustrated in chlorideform, include octyl chloride, butenyl chloride, hexynyl chloride,ethoxydecyl chloride, vinoxyethyl chloride, hydroxyethyl chloride,benzyl chloride, phenylbutenyl chloride, butylphenylethyl chloride,meth- ,oxybenzyl chloride, dodecoxybenzyl chloride, methoxybutylbenzylchloride, octylphenoxyethyl chloride, cyanobenzyl chloride, bromo-benzylchloride. nitrobenzyl chloride, methyl chloroacetate, chlorobutylacetate, benzyl chloropropionate, octyl chloromethylbenzoate, chlorobutanamide, chloro methyl methyl ketone, and chlorodecyl phenyl ketone.Typical representations of the substituted aminoacetamidoximes includediethylaminoacetamidoxime, morpholinopropionamidoxime,dimethylaminoacetamidoxime, pyrrolidinoacetamidoxime,piperidinoacetamidoxime and morpholinoacetamidoxime.

The quaternary ammonium compounds of this invention are prepared bybringing together the selected reactants at a reacting temperature inthe range of about 20 C. to the reflux temperature of the reactantmixture,

preferably not above about 200 C. The preferred range is about 25 to 100C. The use of an inert volatile solvent is advantageous and in thisrespect, there may be employed methanol, ethanol, isopropanol,tert-butanol,

diethyl ether, acetonitrile, formamide, dioxane, dimethylformamide,nitromethane, ethylene glycol, toluene, and

V the like.

Reaction times of. about two to twenty-four hours and more are generallyemployed depending largely on the reaction temperature, use and identityof a solvent, and

"the particular reactants employed. The time of reaction not criticalbut merely influences the yield. As will be apparent to one skilled inthe art, the longer reaction times generally favor higher yields, up toa point. Also, some reactants combine more speedily than others. Inorder to assure completeness of reaction and concomitant substantiallyquantitative results, if desired, there may be determined the amount ofionizable anion, particularly when halide is involved. When thetheoretical amount of anion is present, the reaction is complete.

The reactants of this invention combine in substantially equimolecularamounts to form the quaternary ammonium products of this invention insubstantially quantitative amounts. Either reactant may be employed inexcess, if desired. It is preferable to employ an excess of R X if one.reactant is desired in excess.

At the conclusion of the reaction, any solvent used may be removed bystripping, preferably under reduced pressure. It is possible, andfrequently advantageous, in the preparation of some of the instantcompounds tofirst prepare the halide form, such as chloride, in a manneralready set forth, and then prepare any other desired form within thepresent definition by metathesis or ion exchange methods. For instance,any of the present compounds in halide form may be converted to thehydroxide form through the use of silver oxide, or the like, and thenconverted to any desired anion form by acidifying with an acid of choicesuch as sulfuric, phosphoric, acetic, and others within the range andspirit of this invention. As an alternative, an anion-exchange resin maybe employed. Any of the present compounds, in halide or bydroxide form,may be converted to any desired anion form through the use of ananion-exchange resin in the desired anion form. For instance, there maybe used an insoluble, cross-linked, styrene-divinylbenzene copolymericquaternary ammonium salt in its sulfate, phosphate, or the like, form toconvert a present compound in halide or hydroxide form to a desiredform, such as sulfate, phosphate, and the like.

It is also possible to make the present quaternary ammonium compounds byquaternary ammonium compounds by quaternizing the correspondingaminoacetonitrile with the reactant R X under the condition describedpreviously and then reacting that quaternary ammonium compound withhydroxylamine. If the hydroxylamine is used in one of its common saltforms, common bases, such as sodium carbonate, sodium hydroxide,potassium carbonate and the like are used to free the hydroxylamine forreaction. The reaction with hydroxylamine is conveniently carried out inaqueous or aqueous lower alkanolic solution at temperatures ranging from0 to C.

The present compounds are produced in yields that constantly approachquantitativeness. They are crystalline compounds or viscous oils andwaxes, that are readily handled by well-known techniques. The presentcompounds are effective bactericides particularly when applied againstMicrococcus pyogenes var. aureus and 'Salmonella typhosa as determinedby standard phenol coelficient tests. The bactericidal effect is highestin those compounds where 'the group R contains from 8 to 21 carbon atomsand these groups are preferred. The instant compounds are usefulfungicides in dilutions down to one-half ounce in gallons of formulationand lower, particularly when applied against Slemphylium sarcinaeformeand Monilina fructicola and evaluated by standard methods.

The compounds of this invention, in particular wherein the R groupcontains from 8 to 21 carbon atoms, are

valuable as detergent-sanitizers and may be employed in meat plants tosanitize cutting table, grinders, and the like, in fruit processingoperations, for instance, to wash and sanitize lemons, oranges, andgrapefruit, and in dairy farms to sanitize dairy equipment and utensils.

A suitable detergent-sanitizer formulation for use in meat plantsincludes, by weight, 5% of a compound of this invention, 2.5 to 5.0% ofoctylphenoxypolyethoxy- H ,ethanol. 20 to 40% soda ash, 20 to.40% sodiummeta- Silicate, and the remainder sodium tripolyphosphate. One ounce ofthis formulation is used per gallon of water. For sanitizing citrusfruit, there is preferably used one part of a present compound in 5000parts of water. For use in dairy farms, there may be used of aquaternary ammonium compound of this invention, 10% ofoctylphenoxypolyethoxyethanol, 7% of trisodium phos- .phate, and 73% ofwaters One ounce of this solution is used per four gallons of water. Thein- .stant compounds in aqueous solution in amounts of about 0.5 to oneounce to one hundred pounds of dry fabric, are excellent as a finaldiaper rinse to prevent diaper rash. These compounds are also excellentpremise the following examples which are offered by way of il lustrationand not by way of limitation. Parts by weigh are used throughout.

Example 1 A mixture is made of 117 parts of dimethylaminoacetamidoxime,202 parts of 5,5,7,7-tetramethyl-2-octenyl 'chloride (dodecenylchloride), and 300 parts of isopropyl alcohol. The mixture is stirred atroom temperature for twenty-four hours. The isopropyl alcohol is removedby stripping under vacuum to yield a gummy solid which is suspended inacetone, filtered and dried. There is recovered a colorless solidmelting at l68-170 C. This product corresponds in analysis toN-5,5,7,7tetra- {methyl 2 octenyl N,N dimethylammoniumacetam- ,idoximechloride.

When 331 parts of 9-octadecenyl bromide is substituted for the5,5,7,7-tetramethyl-2-octenyl chloride in the above preparation, thereis obtained a viscous oil, characterized asN-9-octadecenyl-N,N-dirnethylammoniumacetamidoxime bromide. 1

Example 2 CHzCH: NOH

0 NCH2C CHzCHz NH! 12H2li In the same way, n-dodecyl bromide is reactedwith a molecular equivalent of dimethylaminoacetamidoxime to give NOH(CHahNCHzC Br 012E125 NH: and with diethylaminoacetamidoxime to giveN-n-dodecyl-N,N-dmimethylammonium acetamidoxime bromide.

In the same way, from 234 parts of dimethylaminoacetamidoxime, 650 partsof octadecyl bromide, and 640 parts ot isopropyl alcohol. there isobtained a soft solid 3 which corresponds in analysis toN-octadecyl-N,N-dimethylammoniumacetamidoxime bromide. It issubstantially water-soluble.

Example 3 A mixture is made of 60 parts of methyltridecylbenzyl chloridewhich is predominantly the 2-methyl-5-tridecyl isomer, 23 parts ofdimethylaminoacetamidoxime and 64 parts of isopropyl alcohol. It isheated at 75 C. (under reflux) for six hours. The isopropyl alcohol isremoved in vacuo to give a tan syrup which is substantia lly soluble inwater. This syrup corersponds in analysis to N methyltridecylbenzyl N,Ndimethylammoniumacetamidoxime chloride.

In the same way, dodecylbenzyl chloride is reacted with a molecularequivalent of piperidinoacetamidoxime to give NOH oimaomiomi 'romo (3H2CH2 CH2 CH2 In the same way, octylbenzyl chloride is reacted with amolecular equivalent of pyrrolidinoacetamidoxime to give Noctylbenzylpyrrolidiniumacetamidoxime chloride andmorpholinopropionamidoxime is reacted with octodecenyl bromide toproduce N-octadecenyl-N-octylammonium propionamidoxime bromide.

Example 4 To an aqueous solution of 44 parts of N-cyanomethyl-N-benzyl-N,Ndimethyl ammonium chloride in 8 parts of water is addedparts of ethanol and then 17.5 parts of hydroxylamine hydrochloridedissolved in 50 parts of water. To the mixture is added slowly asolution of 13.3 parts of sodium carbonate in 50 parts of water. Themixture is stirred for two to three hours. It is evaporated to drynessin vacuo. The solid is extracted with 300 parts of dry ethyl acetate andfiltered. The residue is dissolved in parts of methanol, filtered toremove salt, and placed in a refrigerator. The colorless product isfiltered. A sample dried in vacuo at 60* C. melts at l76-l78 C. Itcorresponds in analysis to N-benzyl-N, N-dimethylammoniumacetamidoximechloride, of the formula NHl The product is outstanding in inhibitingthe growth of .Stemphyliium sarcinaeforme and Monilinia fructicola.

In a similar manner, from N-cyanomethyl-N-allyl-N, N-dimethylammoniumchloride, hydroxylamine hydrochloride, and sodium carbonate insubstantially equivalent amounts, there is obtainedallyldimethylammoniumacetamidoxime chloride as a colorless crystallinesolid.

Example 5 for the benzyl chloride in above procedure there is obtained ayellow solid corresponding in composition top-nitrobenzyldimethylammoniumacetamidoxime chloride.

When 24 parts of octylphenoxyethyl bromide is substituted for the benzylchloride, there is obtained an alcoholic solution of the quaternaryammonium salt having 1 the formula:

/NOH 051117051140CHQCHQN(CH3)2CH2C ]Bl- NH It is extremely bactericidaltowards M icrococcus pyogenes var. aureus.

When- 19.5 parts of 2,4-dichlorobenzyl chloride is substituted for thebenzyl chloride in the above procedure there is obtained on evaporationa colorless solid corresponding in composition to2,4-dichlorobenzyldimethylammoniumacetamidoxime chloride.

When 16.7 parts of phenylbutenyl chloride is substiway tuted for thebenzyl chloride in the above procedure,

there is obtained an alcohol solution of the compound:

N011 [CeHCHzCH=CHCHzN(CHa)2CH2C\ :lCl-

NH: This solution strikingly inhibits the growth of Stemphyliumsarcinaeforme.

When 12 parts of propargyl bromide is substituted for the benzylchloride in the above procedure, there is obtainedpropargyldimethylammoniumacetamidoxime bromide.

When 12.5 parts of ethylene bromohydrin is substituted for the benzylchloride in the above procedure, there is obtained a thick oil whichcorresponds in composition to the structure NHz When 19 parts ofoctyloxyethyl chloride is substituted for benzyl chloride in the aboveexample, there is obtained a water-soluble oil which has the structure:

NOH CsH17OCH2CH2N(CH3)2CH2C. ]Cl i: \N'H2 When 14 parts of methyl iodideis substituted for benzyl chloride in the above example, there isobtained a colorless crystalline solid which is water-soluble andcorresponds in composition to trimethylammoniumacetarnidoxime iodide.

When 31 parts of 4-dodecyloxybenzyl chloride is substituted for benzylchloride in the above example, there is obtained a viscous oil which iswater-soluble and has effective bactericidal and surface activeproperties. It corresponds in structure toN-4-dodecoxybenzyl-N,N-dimethylammoniurnacetamidoxime chloride.

When 20 parts of phenoxyethyl bromide is substituted for benzy lchloride in the above examples there is obtained a crystalline solidwhich corresponds in structure tophenoxyethy-ldimethylammoniumacetamidoxime bromide.

When 13 parts of bromoacetamide is substituted for benzylchloride in theabove example, there is obtained 'N carbamoylmethyl N,Ndimethylammoniumacetamidoxime bromide.

When 16 parts of phenacyl chloride ar substituted for benzyl chloride inthe above example, there is obtainedphenacyldimethylammoniumacetarnidoxime chloride, of

the structure:

Chloromethyl heptadecyl ketone can be used in the same to provideN-heptadecylcarbonylmethyl-N',N-dimethyannnoniumacetamidoxime chloride,

When 17 parts of ethyl bromoacetate is substituted for 'benzyl chloridein the above example, there is obtained N ethoxycarbonylmethyl N',Ndimethylammoniumacetamidoxirne bromide.

When 39 parts of 2-bro-rnoethyl stearate is substituted in which R and Rconsidered singularly are alkyl'groups of l to 2 carbon atoms andconsidered collectiveiy'represent a divalentsaturated chain that formswith the amino nitrogen atom a 5 to 6 membered heteromonocyclicamineselected from the group consisting of pyrrolidinyl, piperidino,morpholino, and thiomorpholino, R? is a member of the class consistingof alkyl of l to 18 carbon atoms, alkenyl of 3 to 18 carbon atoms,alkynyl of 3 to 18 carbon atoms, alkenoxyalkyl of 3 to 20 carbon atomsin which the alkenoxy group is located on the alkyl group in a positionof remoteness of at least beta with respect to the amino nitrogen atom,alkoxyalkyl of 3 to 20 car bon atoms in which the alkoxy group islocated on the alkyl group in a position of remoteness of at least betawith respect to the amino nitrogen atom, hydroxyalkyl of 2 to 18 carbonatoms in which the hydroxy group is located on the alkyl group in aposition of remoteness of at least beta with respect to the aminonitrogen atom,

alkoxyarylalkyl having up to 21 carbon atoms, aryloxyalkyl having up to21 carbon atoms, alkyl'aryloxyalkyl having up to 21 carbon atoms,arylalkyl of 7 to 21 carbon atoms, alkylarylalkyl of 8 to 21 carbonatoms, arylalkenyl of 8 to 21 carbon atoms, carbamoylalkyl of 2 to 18car- 'bon atoms, alkoxycarbonylalkyl of 3 to 20 carbon atoms,

acyloxyalkyl of 3 to 20 carbon atoms, alkylcarbonylalkyl of 3 to 20carbon atoms and arylcarbonylalkyl of 8 to 20 2-octenyl-N,N-dimethylammoniumacetamidoxime chloride.

3. A composition of matter having the formula Nome 1 NOH Br CHZCH?dodecyl NH2 4. A composition of matter having the formula dodecyl N H:

5. As a composition of matter N-methyltridecylbenzyl-N,N-dimethyl-ammoniumacetamidoxime chloride.

6. As a composition of matter N-benzyl-N,N-dimethylammoniumacetamidoximechloride.

References Cited in the file of this patent UNITED STATES PATENTS2,851,457 Zimmermann Sept. 9, 1958 Burtner Apr. 27; 1954v

1. AS A COMPOSITION OF MATTER THE COMPOUND HAVING THE FORMULA
 3. ACOMPOSITION OF MATTER THE FORMULA